This Pancreatic Adenocarcinoma (Cancer) SPORE will greatly strengthen and expand the pancreatic cancer research of the UAB Comprehensive Cancer Center with an emphasis on translational research. Its themes of Gene Therapy, Death Receptor Targeted Immunotherapy, Growth Factor Mechanisms of chemoresistance, and mechanisms of Tumor Gene Suppression and Protein Degradation are all a critical priority. Four research projects involve interdisciplinary investigative teams including: 1.) "Cytotoxic Resistance: FGFR-1 Signaling and Reversion" which will explore the mechanism of FGFR-1 differential signal transduction and its resistance to cytotoxic insulin (CR) in cytotoxic (chemoradiation) resistance demonstrated in clinical pancreatic cancer. 2.) "Mechanisms of Tumor Suppressor DPC4/Smad4for Protein Instability in Pancreatic Cancer" which will evaluate the role of Jab-1 inhibition and Smad4/DPC4 protein degradation as potential inhibitor of pancreatic tumor growth. 3.) "Multimodality Targeted Therapy of Pancreatic Cancer - Use of Death Receptor (DR) Antibodies Alone and in Combination with Chemotherapy-Radiation Interactions" which will provide early translation for targeted immunotherapy to treat pancreatic cancer via anti DR5 death receptor antibody TR-8 (Anti-DR5). 4.) "Coordinated Virus - Adjunctive therapies (CVAT) for Pancreatic Cancer" which will be a fundamental development and selection of novel gene therapy vectors including early translation trial involving RAID supported conditionally replicative RGD-COX-2 adenoviral vector and a FDA approved HSV 207 oncolytic herpes vector. These projects will be supported by four Cores: 1.) Administrative/Biostatistics Core; 2.) Tissue Resource & Immunopathology Core; 3.) Clinical Core, and 4.) Animal Model and Imaging Core. In addition, the SPORE will have a Career Development Program directed at careers in Pancreatic Cancer Translational Research (5 awards) and a Developmental Research Program (4 pilot projects annually). The SPORE has strong institutional commitments and enthusiastic plans for interaction with other SPOREs including our own Brain, Breast, and Ovarian Cancer SPORE. This SPORE will increase scientific discoveries and rapidly translate findings into innovative clinical trials.